Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The crystal structures of four inhibitor complexes of dialkylglycine decarboxylase are reported. The enzyme does not undergo a domain closure, as does aspartate aminotransferase, upon inhibitor binding. Two active-site conformations have been observed in previous structures that differ in alkali metal ion content, and two active-site conformations have been shown to coexist in solution when a single type of metal ion is present. There is no indication of coexisting conformers in the structures reported here or in the previously reported structures, and the observed conformation is that expected based on the presence of potassium in the enzyme. Thus, although two active-site conformations coexist in solution, a single conformation, corresponding to the more active enzyme, predominates in the crystal. The structure of 1-aminocyclopropane-1-carboxylate bound in the active site shows the aldimine double bond to the pyridoxal phosphate cofactor to be fully out of the plane of the coenzyme ring, whereas the Calpha-CO2(-) bond lies close to it. This provides an explanation for the observed lack of decarboxylation reactivity with this amino acid. The carboxylate groups of both 1-aminocyclopropane-1-carboxylate and 5'-phosphopyridoxyl-2-methylalanine interact with Ser215 and Arg406 as previously proposed. This demonstrates structurally that alternative binding modes, which constitute substrate inhibition, occur in the decarboxylation half-reaction. The structures of d and l-cycloserine bound to the active-site show that the l-isomer is deprotonated at C(alpha), presumably by Lys272, while the d-isomer is not. This difference explains the approximately 3000-fold greater potency of the l versus the d-isomer as a competitive inhibitor of dialkylglycine decarboxylase.
 ...
PMID:Crystal structures of dialkylglycine decarboxylase inhibitor complexes. 1055 38

Despite the extensive amount of research conducted on mourning doves (Zenaida macroura), no biochemical reference values exist for this species. Our objective, therefore, was to establish base line clinical chemistry reference values for mourning doves to assist with establishing clinical diagnoses. Wild mourning doves were captured 19 March 1996 to 8 August 1996, and 6 February 1998 to 12 May 1998; blood samples were collected from 382 mourning doves. Plasma biochemical values were established for glucose, sodium, potassium, chloride, enzymatic CO2, albumin, total protein, globulin, calcium, phosphorus, cholesterol, magnesium, aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), and uric acid. These reference values are invaluable for determining diagnosis of diseases of the gastrointestinal, hepatic, renal, cardiovascular, musculoskeletal, and endocrine systems.
 ...
PMID:Blood plasma chemistries from wild mourning doves held in captivity. 1094 41

In the present study, effects of enrofloxacin on biochemical, haematological and blood gas parameters were investigated. Changes in laboratory parameters were monitored during the treatment period. Enrofloxacin was administered (5 mg/kg intramuscularly, once daily) to 10 healthy dogs for 14 days. Acidosis and temporary increases in aspartate aminotransferase, indirect bilirubin, sodium, partial pressure of CO2 and mean corpuscular volume levels as well as decreased levels of inorganic phosphorus, ionized calcium, potassium, partial pressure of O2 and standard bicarbonate were observed. The results of this study suggest that these observed effects of enrofloxacin on blood gas parameters should be taken into consideration in long-term use of the drug.
 ...
PMID:Investigation of biochemical and haematological side-effects of enrofloxacin in dogs. 1151 13

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide, and iron. HO-1, an inducible form, is thought to contribute to resistance to various types of oxidative stress. Doxorubicin (DOX) produces clinically useful responses in a variety of human cancers. We reported previously that prior administration of DOX ameliorated subsequent hepatic ischemia and reperfusion injury. The aim of this study was to examine whether this pharmacological preconditioning was useful for another type of hepatic injury induced by a non-surgical method. When a high dose of DOX (10 mg/kg body weight) was administered directly to rat liver via the portal vein, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels increased markedly 24 hr after the injection. Under this condition, zinc-protoporphyrin IX, a specific inhibitor of HO-1, caused both serum AST and ALT levels to be elevated further. When a low dose of DOX (5 mg/kg body weight) was administered to rats via the tail vein as pharmacological preconditioning 3 days before the injection of a high dose of DOX via the portal vein, the levels of serum AST and ALT in rats clearly were improved as compared with rats without the preconditioning. Expression of HO-1 in the liver was confirmed 3 days after the administration of a low dose of DOX. In addition, prior administration of zinc-protoporphyrin IX abolished the effect of DOX preconditioning. Immunohistochemical analysis showed that the positive staining of HO-1 protein induced by a low dose of DOX was localized to histiocytes infiltrating periportal areas. These results strongly suggest that pharmacological preconditioning with DOX may generally help to attenuate subsequent oxidant-induced hepatic injury.
 ...
PMID:Pharmacological preconditioning with doxorubicin. Implications of heme oxygenase-1 induction in doxorubicin-induced hepatic injury in rats. 1170 58

Blood samples were collected from 29 juvenile red pacu (Piaractus brachypomus), ornamental freshwater fish, to establish baseline blood chemistry values. Mean (minimum-maximum) values, obtained by automated bichromatic analysis and ion selective electrode analysis, were as follows: sodium, 150.4 (146-159) mmol/L; potassium, 3.93 (2.7-5.0) mmol/L; chloride, 138.7 (128-150) mmol/L; total CO2, 7.5 (6-10) mmol/L; albumin, 0.86 (0.5-1.0) g/dL; lactate dehydrogenase, 237.8 (65-692) IU/L; aspartate aminotransferase, 49.1 (0-125) IU/L; creatinine, 0.31 (0.2-0.4) mg/dL; calcium, 10.80 (9.5-12.5) mg/dL; anion gap, 6.89 (1.2-12.5) mmol/L; and phosphorus, 7.29 (4.1-8.9) mg/dL.
 ...
PMID:Blood chemistry values of juvenile red pacu (Piaractus brachypomus). 1202 15

The metabolism of biogenic amines and blood chemistry of psychiatric patients were investigated. Eighty newly admitted psychiatric patients suffering from schizophrenia, hypomania, mania and paranoid disorder, and matched with fifteen normal subjects were used for the study. Blood was collected and centrifuged, after which serum was extracted. Serum concentrations of biogenic amines, namely epinephrine, norepinephrine, dopamine and serotonin were determined using spectrofluorimetric method. Serum concentration of 5-HIAA, activities of alanine transaminase and aspartate transaminase were determined. The concentrations of serum protein, albumin, Na+, K+, Cl- and CO2 in the psychiatric patients and control subjects were determined using Synchron CX5 automated spectrophotometer. Results of the study showed that the concentrations of serum epinephrine and norepinephrine in the psychiatric patients were significantly increased, while the concentrations of dopamine and serotonin were significantly decreased, as compared with the controls. Serum 5-HIAA levels were significantly elevated in all psychiatric patients compared with the controls. There was a marked elevation of the activities of alanine transaminase and aspartate transaminase in all psychiatric syndromes, with the exception of paranoid disorder, which was reduced. Data of the study indicate that metabolism of biogenic amines and concentrations of serum proteins, enzymes and some electrolytes were significantly affected in psychiatric patients suffering form schizophrenia, hypomania, mania and paranoid disorder.
 ...
PMID:Biogenic amines metabolism and blood chemistry of psychiatric patients. 1451 Jan 2

Substantial fluid shifts occur during liposuction as wetting solution is infiltrated subcutaneously and fat is evacuated, causing potential electrolyte imbalances. In the porcine model for large-volume liposuction, plasma aspartate aminotransferase and alanine transaminase levels were elevated following liposuction. These results raised concerns for possible mechanical injury and/or lidocaine-induced hepatocellular toxicity in a clinical setting. The first objective of this human model study was to explore the effect of the liposuction procedure on electrolyte balance. The second objective was to determine whether elevated plasma aminotransferase levels were observed subsequent to large-volume liposuction. Five female volunteers underwent three-stage, ultrasound-assisted liposuction. Blood samples were collected perioperatively. Plasma levels of sodium, potassium, venous carbon dioxide, blood urea nitrogen, chloride, and creatinine were determined. Liver function analyte levels were measured, including albumin, total protein, aspartate aminotransferase, and alanine transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase, and total bilirubin. To further define intracellular enzyme release, creatine kinase levels were measured. Mild hyponatremia was evident postoperatively (134 to 136 mmol/liter) in four patients. Hypokalemia was evident intraoperatively in all subjects (mean +/- SEM; 3.3 +/- 0.16 mmol/liter; range, 3.0 to 3.4 mmol/liter). Hypoalbuminemia and hypoproteinemia were observed throughout the study (baseline: 2.9 +/- 0.2 g/dl; range, 2.6 to 3.5 g/dl), decreasing to 10 to 40 percent 24 hours postoperatively (2.0 +/- 0.2 g/dl; range, 1.7 to 2.1 g/dl). Aspartate aminotransferase, alanine transaminase, and creatine kinase levels were significantly elevated after the procedure (190 +/- 47.1 U/liter, 50 +/- 7.7 U/liter, and 11,219 +/- 2556.7 U/liter, respectively) (p < 0.01). Release of antidiuretic hormone and even mildly hypotonic intravenous fluid infiltration have long been known to cause hyponatremia postoperatively. Intraoperative hypokalemia is associated with hypocarbia and respiratory alkalosis and the elevated epinephrine levels observed in the concurrent study. Factors having the greatest initial impact on diminished serum albumin and protein levels postoperatively are redistribution and hemodilution. Subsequent diminished viscosity may significantly affect postoperative hemodynamics. Elevated aspartate aminotransferase, alanine transaminase, and creatine kinase levels are associated with skeletal muscle injury, adipocyte lysis, and/or hepatic damage. Therefore, tissue injury is associated with large-volume liposuction as observed in several cellularly released enzymes. Future clinical studies are required to determine the degree of injury and specific tissues that are damaged or sensitive to mechanical trauma and/or drugs used in large-volume liposuction.
 ...
PMID:Electrolyte and plasma enzyme analyses during large-volume liposuction. 1531 60

To investigate whether hypercapnic acidosis, induced by adding CO2 to inspired gas, would be protective effect against ventilator-induced lung injury (VILI), we ventilated 55 normal white rabbits for 6 hr or until PaO2/FIO2 <200 mmHg. Control group (n=15) was ventilated with peak inspiratory pressure (PIP) of 15 cm H2O, positive end-expiratory pressure (PEEP) of 3 cm H2O, an inspiration-to-expiration ratio of 1:2, and an inspired oxygen fraction (FIO2) of 0.40. High pressure hypercapnic group (HPHC; n=20) was ventilated with PIP of 30 cm H2O, PEEP of 0 cm H2O, and FIO2 of 0.40. Carbon dioxide was introduced into the inspiratory limb of the ventilator circuit, as necessary to maintain hypercapnia (PaCO2, 65 to 75 mmHg). High pressure normocapnic group (HPNC; n=20) was ventilated with same setting of HPHC, except normocapnia (PaCO2, 35 to 45 mmHg). Bronchoalveolar lavage fluid (BALF) lactate dehydrogenase, aspartate aminotransferase, interleukin-8 were significantly higher in high pressure ventilator group than control group (p<0.05). Wet weight to dry weight (WW/DW) and histologic scores were significantly higher in high pressure ventilator group than control group (p<0.05). However, there were no significant differences in oxygenation, BALF inflammatory markers, WW/DW and histologic scores between HPHC and HPNC groups. These findings suggest that hypercapnic acidosis at least induced by CO2 insufflation would not be protective effect against VILI in this model.
 ...
PMID:Does hypercapnic acidosis, induced by adding CO2 to inspired gas, have protective effect in a ventilator-induced lung injury? 1622 49

Standard hematologic and serum chemistry parameters were determined from 28 harp seals (Phoca groenlandica) and 20 hooded seals (Cystophora cristata) sampled from 6 March 2001 to 13 March 2001 during the breeding season. Whole blood was collected immediately postmortem from harp seal mother-pup pairs and from six hooded seal pups, and from live-captured adult hooded seals and three hooded seal pups; blood was analyzed within 24 hr at a local human hospital. A certified veterinary laboratory validated subsamples of whole blood and analyzed all serum chemistry parameters. Significant interlaboratory differences in mean values of packed cell volume (PCV) and mean cell volume (MCV) were found. Significant differences were found between samples from the five seal groups (adult male hooded seals, lactating female hooded seals, unweaned hooded seal pups; lactating female harp seals, and unweaned harp seal pups) for hematology and most serum chemistry parameters. In general, age-class influenced mean values of PCV, hemoglobin (HB), red blood cell (RBC) counts, MCV, mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), and nucleated red blood cell (NRBC) counts per 100 leucocytes, but most age-related variations were species specific. Harp seal pups had significantly lower mean values of HB, PCV, MCH, and MCHC than did other seal groups, and significantly lower mean RBC counts than did hooded seal pups. Mean NRBC counts per 100 leukocytes were more than three times higher in harp seal pups than in hooded seal pups, but this difference was not statistically significant. Mean MCV were significantly lower in harp and hooded seal pups compared to those of adult harp and hooded seals. Differences in hemograms between pup species were likely because of the precocious development of hooded seal pups, which are weaned within 4 days, compared to 12 days for harp seal pups. Among adult seal groups, male hooded seals had significantly higher mean values of PCV and HB than did female harp and hooded seals, and significantly higher mean RBC counts than did adult female hooded seals. Among adult females, mean values of MCH and MCHC were statistically higher in hooded seals than in harp seals. Adult female harp and hooded seals did not differ significantly in other RBC parameters and mean leukocyte counts. Mean values of glucose, blood urea nitrogen, total bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein, and albumin showed species-specific variations between adults and pups. Except for ALP, few significant differences in mean enzyme activities of aspartate aminotransferase (AST), ALT, creatine kinase and gamma-glutamyltransferase were found between seal groups. Mean concentrations of electrolytes (calcium, phosphorus, sodium, potassium, chloride, magnesium, and total carbon dioxide) varied with age class, but variations in potassium and magnesium were species specific. Harp seal pups had significantly higher mean phosphorus and potassium levels compared to other seal groups.
 ...
PMID:Hematology and serum chemistry of harp (Phoca groenlandica) and hooded seals (Cystophora cristata) during the breeding season, in the Gulf of St. Lawrence, Canada. 1669 54

In the pyrimidine biosynthetic pathway, N-carbamyl-L-aspartate (CA-asp) is converted to L-dihydroorotate (DHO) by dihydroorotase (DHOase). The mechanism of this important reaction was probed using primary and secondary 15N and 13C isotope effects on the ring opening of DHO using isotope ratio mass spectrometry (IRMS). The reaction was performed at three different temperatures (25, 37, and 45 degrees C for hamster DHOase; 37, 50, and 60 degrees C for Bacillus caldolyticus), and the product CA-asp was purified for analysis. The primary and secondary kinetic isotope effects for the ring opening of the DHO were determined from analysis of the N and C of the carbamyl group after hydrolysis. In addition, the beta-carboxyl of the residual aspartate was liberated enzymatically by transamination to oxaloacetate with aspartate aminotransferase and then decarboxylation with oxaloacetate decarboxylase. The 13C/12C ratio from the released CO2 was determined by IRMS, yielding a second primary isotope effect. The primary and secondary isotope effects for the reaction catalyzed by DHOase showed little variation between enzymes or temperatures, the primary 13C and 15N isotope effects being approximately 1% on average, while the secondary 13C isotope effect is negligible or very slightly normal (>1.0000). These data indicate that the chemistry is at least partially rate-limiting while the secondary isotope effects suggest that the transition state may have lost some bending and torsional modes leading to a slight lessening of bond stiffness at the carbonyl carbon of the amide of CA-asp. The equilibrium isotope effects for DHO --> CA-asp have also been measured (secondary 13K(eq) = 1.0028 +/- 0.0002, primary 13K(eq) = 1.0053 +/- 0.0003, primary 15K(eq) = 1.0027 +/- 0.0003). Using these equilibrium isotope effects, the kinetic isotope effects for the physiological reaction (CA-asp --> DHO) have been calculated. These values indicate that the carbon of the amide group is more stiffly bonded in DHO while the slightly lesser, but still normal, values of the primary kinetic isotope effect show that the chemistry remains at least partially rate-limiting for the physiological reaction. It appears that the ring opening and closing is the slow step of the reaction.
 ...
PMID:13C and 15N isotope effects for conversion of L-dihydroorotate to N-carbamyl-L-aspartate using dihydroorotase from hamster and Bacillus caldolyticus. 1675 3


<< Previous 1 2 3 4 5 6 7 8 9 Next >>